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Journal ArticleDOI

Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2.

TL;DR: There was a wide spectrum of presenting signs and symptoms and disease severity, ranging from fever and inflammation to myocardial injury, shock, and development of coronary artery aneurysms, and comparison with the characteristics of other pediatric inflammatory disorders.
Abstract: Importance In communities with high rates of coronavirus disease 2019, reports have emerged of children with an unusual syndrome of fever and inflammation. Objectives To describe the clinical and laboratory characteristics of hospitalized children who met criteria for the pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) and compare these characteristics with other pediatric inflammatory disorders. Design, Setting, and Participants Case series of 58 children from 8 hospitals in England admitted between March 23 and May 16, 2020, with persistent fever and laboratory evidence of inflammation meeting published definitions for PIMS-TS. The final date of follow-up was May 22, 2020. Clinical and laboratory characteristics were abstracted by medical record review, and were compared with clinical characteristics of patients with Kawasaki disease (KD) (n = 1132), KD shock syndrome (n = 45), and toxic shock syndrome (n = 37) who had been admitted to hospitals in Europe and the US from 2002 to 2019. Exposures Signs and symptoms and laboratory and imaging findings of children who met definitional criteria for PIMS-TS from the UK, the US, and World Health Organization. Main Outcomes and Measures Clinical, laboratory, and imaging characteristics of children meeting definitional criteria for PIMS-TS, and comparison with the characteristics of other pediatric inflammatory disorders. Results Fifty-eight children (median age, 9 years [interquartile range {IQR}, 5.7-14]; 20 girls [34%]) were identified who met the criteria for PIMS-TS. Results from SARS-CoV-2 polymerase chain reaction tests were positive in 15 of 58 patients (26%) and SARS-CoV-2 IgG test results were positive in 40 of 46 (87%). In total, 45 of 58 patients (78%) had evidence of current or prior SARS-CoV-2 infection. All children presented with fever and nonspecific symptoms, including vomiting (26/58 [45%]), abdominal pain (31/58 [53%]), and diarrhea (30/58 [52%]). Rash was present in 30 of 58 (52%), and conjunctival injection in 26 of 58 (45%) cases. Laboratory evaluation was consistent with marked inflammation, for example, C-reactive protein (229 mg/L [IQR, 156-338], assessed in 58 of 58) and ferritin (610 μg/L [IQR, 359-1280], assessed in 53 of 58). Of the 58 children, 29 developed shock (with biochemical evidence of myocardial dysfunction) and required inotropic support and fluid resuscitation (including 23/29 [79%] who received mechanical ventilation); 13 met the American Heart Association definition of KD, and 23 had fever and inflammation without features of shock or KD. Eight patients (14%) developed coronary artery dilatation or aneurysm. Comparison of PIMS-TS with KD and with KD shock syndrome showed differences in clinical and laboratory features, including older age (median age, 9 years [IQR, 5.7-14] vs 2.7 years [IQR, 1.4-4.7] and 3.8 years [IQR, 0.2-18], respectively), and greater elevation of inflammatory markers such as C-reactive protein (median, 229 mg/L [IQR 156-338] vs 67 mg/L [IQR, 40-150 mg/L] and 193 mg/L [IQR, 83-237], respectively). Conclusions and Relevance In this case series of hospitalized children who met criteria for PIMS-TS, there was a wide spectrum of presenting signs and symptoms and disease severity, ranging from fever and inflammation to myocardial injury, shock, and development of coronary artery aneurysms. The comparison with patients with KD and KD shock syndrome provides insights into this syndrome, and suggests this disorder differs from other pediatric inflammatory entities.

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Journal ArticleDOI
25 Aug 2020-JAMA
TL;DR: This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19, the novel severe acute respiratory syndrome coronavirus 2 pandemic that has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease.
Abstract: Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

3,371 citations

Journal ArticleDOI
TL;DR: Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS, and a similar outbreak of Kawasaki-like disease is expected in countries involved in the SEMS epidemic.

1,851 citations

Journal ArticleDOI
TL;DR: Community-level intervention and prevention efforts, including health communication strategies, designed to reach these groups could help address various mental health conditions associated with the COVID-19 pandemic.
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has been associated with mental health challenges related to the morbidity and mortality caused by the disease and to mitigation activities, including the impact of physical distancing and stay-at-home orders.* Symptoms of anxiety disorder and depressive disorder increased considerably in the United States during April-June of 2020, compared with the same period in 2019 (1,2). To assess mental health, substance use, and suicidal ideation during the pandemic, representative panel surveys were conducted among adults aged ≥18 years across the United States during June 24-30, 2020. Overall, 40.9% of respondents reported at least one adverse mental or behavioral health condition, including symptoms of anxiety disorder or depressive disorder (30.9%), symptoms of a trauma- and stressor-related disorder (TSRD) related to the pandemic† (26.3%), and having started or increased substance use to cope with stress or emotions related to COVID-19 (13.3%). The percentage of respondents who reported having seriously considered suicide in the 30 days before completing the survey (10.7%) was significantly higher among respondents aged 18-24 years (25.5%), minority racial/ethnic groups (Hispanic respondents [18.6%], non-Hispanic black [black] respondents [15.1%]), self-reported unpaid caregivers for adults§ (30.7%), and essential workers¶ (21.7%). Community-level intervention and prevention efforts, including health communication strategies, designed to reach these groups could help address various mental health conditions associated with the COVID-19 pandemic.

1,799 citations

Journal ArticleDOI
TL;DR: The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction.
Abstract: Background A multisystem inflammatory syndrome in children (MIS-C) is associated with coronavirus disease 2019 The New York State Department of Health (NYSDOH) established active, statewi

1,012 citations

Journal ArticleDOI
11 Mar 2020-JAMA
TL;DR: The COVID-19 Treatment Guidelines Panel recommends using an N95 respirator (or equivalent or higher-level respirator) rather than surgical masks, in addition to other personal protective equipment (PPE) (i.e., gloves, gown, and eye protection such as a face shield or safety goggles).
Abstract: Recommendations Infection Control • For health care workers who are performing aerosol-generating procedures on patients with COVID-19, the COVID-19 Treatment Guidelines Panel (the Panel) recommends using an N95 respirator (or equivalent or higher-level respirator) rather than surgical masks, in addition to other personal protective equipment (PPE) (i.e., gloves, gown, and eye protection such as a face shield or safety goggles) (AIII). • The Panel recommends minimizing the use of aerosol-generating procedures on intensive care unit patients with COVID-19 and carrying out any necessary aerosol-generating procedures in a negative-pressure room, also known as an airborne infection isolation room, when available (AIII). • For health care workers who are providing usual care for nonventilated patients with COVID-19, the Panel recommends using an N95 respirator (or equivalent or higher-level respirator) or a surgical mask in addition to other PPE (i.e., gloves, gown, and eye protection such as a face shield or safety goggles) (AII). • For health care workers who are performing non-aerosol-generating procedures on patients with COVID-19 who are on closed-circuit mechanical ventilation, the Panel recommends using an N95 respirator (or equivalent or higher-level respirator) in addition to other PPE (i.e., gloves, gown, and eye protection such as a face shield or safety goggles) because ventilator circuits may become disrupted unexpectedly (BIII). • The Panel recommends that endotracheal intubation in patients with COVID-19 be performed by health care providers with extensive airway management experience, if possible (AIII). • The Panel recommends that intubation be performed using video laryngoscopy, if possible (CIII).

587 citations

References
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Journal ArticleDOI
TL;DR: These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances.
Abstract: Background: Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acqui...

2,139 citations

Journal ArticleDOI
TL;DR: Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS, and a similar outbreak of Kawasaki-like disease is expected in countries involved in the SEMS epidemic.

1,851 citations


Additional excerpts

  • ...Respiratory Intubation 25 (43) 2 (9) 23 (79) 2 (7) 5 (38) 20 (44) 1 (14) 24 (47) 5 (63) 20 (40) 20 (45) 5 (36) Pharmacotherapy Intravenous immunoglobulin 41 (71) 14 (61) 21 (72) 20 (69) 13 (100) 28 (62) 7 (100) 34 (68) 8 (100) 33 (66) 33 (75) 8 (57) Corticosteroids 37 (64) 12 (52) 19 (66) 18 (62) 12 (92) 25 (56) 7 (100) 30 (59) 7 (88) 30 (60) 33 (75) 4 (29) Anakinra (IL-1 receptor antagonist) 3 (5) 1 (4) 2 (7) 1 (3....

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  • ...Headache 15 (26) 4 (17) 11 (38) 4 (14) 4 (31) 11 (24) 1 (14) 14 (27) 4 (50) 11 (22) 13 (30) 2 (14) Respiratory symptoms 12 (21) 2 (13) 9 (31) 3 (10) 3 (23) 9 (20) 1 (14) 11 (22) 3 (38) 9 (18) 9 (20) 3 (21) Lymphadenopathy 9 (16) 3 (13) 2 (7) 7 (24) 5 (38) 4 (9) 4 (57) 5 (10) 2 (33) 7 (14) 8 (18) 1 (7) Swollen hands and feet 9 (16) 2 (13) 4 (14) 5 (17) 4 (31) 5 (11) 4 (57) 5 (10) 1 (17) 7 (14) 7 (16) 2 (14) Sore throat 6 (10) 1 (4) 5 (17) 1 (3) 0 6 (13) 0 6 (12) 1 (17) 5 (10) 6 (14) 0 Confusion 5 (9) 0 5 (17) 0 1 (8) 4 (9) 0 5 (10) 1 (17) 4 (8) 5 (11) 0 Abbreviations: IQR, interquartile range; PIMS-TS, pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2....

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  • ...of immunomodulatory agents 2i 35 (60) 11 (48) 18 (62) 17 (59) 12 (92) 23 (51) 7 (100) 28 (55) 7 (88) 28 (56) 32 (71) 3 (23) 3j 9 (16) 4 (17) 3 (10) 6 (21) 4 (31) 5 (11) 3 (43) 6 (12) 3 (38) 6 (12) 8 (18) 1 (8) Outcomes Coronary artery aneurysm (z score >2) 8 (14) 1 (4) 5 (17) 3 (10) 8 (62) 0 1 (14) 7 (14) 8 (100) 0 6 (13) 2 (15)...

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Journal ArticleDOI

1,840 citations


"Clinical Characteristics of 58 Chil..." refers methods in this paper

  • ...Death 1 (2) 0 1 (3) 0 0 1 (2) 0 1 (2) 0 1 (2) 1 (2) 0 Abbreviations: PIMS-TS, pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF, tumor necrosis factor....

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  • ...10 Clinical patterns were established after review of numerous cases and included (1) a group with shock (inotrope use or fluid resuscitation >20 mL/kg); (2) a group that met criteria for KD; and (3) a group with fever and inflammation who did not have shock or did not meet the clinical criteria for KD....

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Journal ArticleDOI
TL;DR: Children may experience an acute cardiac decompensation caused by severe inflammatory state after SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention.
Abstract: Background: Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children...

869 citations

Journal ArticleDOI
TL;DR: It is determined that anti-spike IgG (S-IgG), in productively infected lungs, causes severe ALI by skewing inflammation-resolving response and providing a potential target for treatment of SARS-CoV or other virus-mediated lung injury.
Abstract: Newly emerging viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome CoVs (MERS-CoV), and H7N9, cause fatal acute lung injury (ALI) by driving hypercytokinemia and aggressive inflammation through mechanisms that remain elusive. In SARS-CoV/macaque models, we determined that anti-spike IgG (S-IgG), in productively infected lungs, causes severe ALI by skewing inflammation-resolving response. Alveolar macrophages underwent functional polarization in acutely infected macaques, demonstrating simultaneously both proinflammatory and wound-healing characteristics. The presence of S-IgG prior to viral clearance, however, abrogated wound-healing responses and promoted MCP1 and IL-8 production and proinflammatory monocyte/macrophage recruitment and accumulation. Critically, patients who eventually died of SARS (hereafter referred to as deceased patients) displayed similarly accumulated pulmonary proinflammatory, absence of wound-healing macrophages, and faster neutralizing antibody responses. Their sera enhanced SARS-CoV-induced MCP1 and IL-8 production by human monocyte-derived wound-healing macrophages, whereas blockade of FcγR reduced such effects. Our findings reveal a mechanism responsible for virus-mediated ALI, define a pathological consequence of viral specific antibody response, and provide a potential target for treatment of SARS-CoV or other virus-mediated lung injury.

751 citations


Additional excerpts

  • ...5) 17 (34) 13 (29) 5 (38) Otherh 6 (10) 2 (9) 3 (10) 3 (10) 1 (8) 5 (11) 1 (14) 5 (10) 0 6 (12) 3 (7) 3 (23) Clinical features at presentationi Abdominal pain 31 (53) 13 (57) 18 (62) 13 (45) 2 (15) 29 (64) 1 (14) 30 (59) 2 (33) 29 (58) 24 (55) 7 (50) Diarrhea 30 (52) 10 (44) 19 (66) 11 (38) 7 (54) 23 (51) 2 (29) 28 (55) 6 (75) 24 (48) 25 (75) 5 (36) Rash 30 (52) 9 (39) 15 (50) 15 (50) 10 (77) 20 (44) 7 (100) 23 (45) 4 (63) 25 (50) 21 (48) 9 (64) Shockd 29 (50) 0 29 (100) 0 6 (46) 23 (51) 1 (14) 28 (55) 6 (75) 23 (46) 25 (56) 4 (31) Vomiting 26 (45) 10 (44) 15 (52) 11 (38) 5 (38) 21 (47) 2 (29) 23 (45) 5 (63) 21 (42) 20 (45) 6 (43) Conjunctival injection 26 (45) 9 (39) 11 (38) 15 (52) 11 (85) 15 (33) 7 (100) 19 (37) 5 (63) 21 (42) 20 (45) 6 (43) Mucous membrane changes 17 (29) 5 (22) 6 (21) 11 (38) 6 (46) 11 (24) 6 (86) 11 (22) 1 (17) 11 (22) 11 (25) 6 (43)...

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  • ...Headache 15 (26) 4 (17) 11 (38) 4 (14) 4 (31) 11 (24) 1 (14) 14 (27) 4 (50) 11 (22) 13 (30) 2 (14) Respiratory symptoms 12 (21) 2 (13) 9 (31) 3 (10) 3 (23) 9 (20) 1 (14) 11 (22) 3 (38) 9 (18) 9 (20) 3 (21) Lymphadenopathy 9 (16) 3 (13) 2 (7) 7 (24) 5 (38) 4 (9) 4 (57) 5 (10) 2 (33) 7 (14) 8 (18) 1 (7) Swollen hands and feet 9 (16) 2 (13) 4 (14) 5 (17) 4 (31) 5 (11) 4 (57) 5 (10) 1 (17) 7 (14) 7 (16) 2 (14) Sore throat 6 (10) 1 (4) 5 (17) 1 (3) 0 6 (13) 0 6 (12) 1 (17) 5 (10) 6 (14) 0 Confusion 5 (9) 0 5 (17) 0 1 (8) 4 (9) 0 5 (10) 1 (17) 4 (8) 5 (11) 0 Abbreviations: IQR, interquartile range; PIMS-TS, pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2....

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  • ...of immunomodulatory agents 2i 35 (60) 11 (48) 18 (62) 17 (59) 12 (92) 23 (51) 7 (100) 28 (55) 7 (88) 28 (56) 32 (71) 3 (23) 3j 9 (16) 4 (17) 3 (10) 6 (21) 4 (31) 5 (11) 3 (43) 6 (12) 3 (38) 6 (12) 8 (18) 1 (8) Outcomes Coronary artery aneurysm (z score >2) 8 (14) 1 (4) 5 (17) 3 (10) 8 (62) 0 1 (14) 7 (14) 8 (100) 0 6 (13) 2 (15)...

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